Vitamin E-stabilized ultrahigh molecular weight polyethylene in joint replacement

doi:10.3969/j.issn.2095-4344.2016.31.021

Abstract

Abstract:

BACKGROUND: As the latest generation of ultrahigh molecular weight polyethylene, vitamin E-stabilized ultrahigh molecular weight polyethylene has been widely put into use of various kinds of joint replacement. However, wear debris and osteolysis caused by that are still the vital factor influencing the clinical curative effect.

OBJECTIVE: To discuss and summarize the material characteristics and application progress of vitamin E-stabilized ultrahigh molecular weight polyethylene, and to seek the theoretical basis which can guide us to launch vitamin E-stabilized ultrahigh molecular weight polyethylene clinically.

METHODS: The first author retrieved the CNKI and Medline databases by computer. The keywords were “ultra-high molecular weight polyethylene, vitamin E-stabilized, joint replacement, application” in English.

RESULTS AND CONCLUSION: Totally 92 articles were retrieved. According to the inclusion and exclusion criteria, 46 articles were included in result analysis. The results show that vitamin E-stabilized ultrahigh molecular weight polyethylene can not only enhance the physicochemical property of prosthesis, but also can integrate with free radicals to increase antioxidant rate of prothesis in order to prolong the long-term curative effect of prosthesis. However, it is still lack of vast of clinical cases and follow-up as evidence. In case of that, long-term clinical efficacy remains to be assessed.

中国组织工程研究杂志出版内容重点：人工关节；骨植入物；脊柱；骨折；内固定；数字化骨科；组织工程

CLC Number:

R318

Xian Jie, He Ben-xiang . Vitamin E-stabilized ultrahigh molecular weight polyethylene in joint replacement[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(31): 4707-4712.

Figures/Tables 1

2.1 聚乙烯材料的发展过程超高分子量聚乙烯是一种高分子聚合物，现在，每年植入的超高分子量聚乙烯人造关节约200万个[13]。对于应用于关节置换中的超高分子量聚乙烯，美国试验材料学会(American Society for Testing and Materials，ASTM)及国际科学组织(International Science Organization)均有明确的要求，这种应用临床的特殊聚乙烯原材料，通常依照分子量的不同被加工成2种不同的聚乙烯粉末，相对分子质量约在3.5×106被加工成GUR1020，而相对分子质量在(5.5-6.0)×106则加工成GUR1050[14]。聚乙烯类的衬垫在20世纪50年代开始被引入髋关节置换中，在1958年，聚四氟乙烯被首先应用于全髋关节置换中，但随后因其较差的耐磨性及分离度而在20世纪60年代被取代。1962年，人们在空气中辐射消毒超高分子量聚乙烯用以强化其物质性质，这是第1代超高分子量聚乙烯[15-16]。尽管最传统超高分子量聚乙烯在物质性质上较聚四氟乙烯有了较大的提高，然而植入物磨损所产生的碎屑仍然是影响手术预后的一大原因，这一问题并没有得到解决。 20世纪80年代，随着科技手段的进一步提高，通过惰性气体消毒，超高分子量聚乙烯的材料性质得到了进一步提高，这是第2代超高分子量聚乙烯。然而这种聚乙烯大多通过聚乙烯分子自由交联，交联程度较低，稳定性较差，交联后的聚乙烯较容易产生降解，关节假体远期存活率较低，使用寿命较短[17]。在20世纪80年代后期，人们越来越认识到磨屑是成为无菌性松动的主要原因之一，加固后的聚乙烯旨在增加假体临床疗效的远期存活率。 20世纪90年代，由Hylamer公司通过改变假体结晶状结构及伸长链来增强超高分子量聚乙烯的物理结构性状及抗磨损性，但关节假体仍发生广泛的磨损及植骨周围出现溶骨反应[18-19]。随着骨关节领域技术的提高，21世纪初出现了一种通过伽马辐射额外交联的超高分子量聚乙烯(第3代超高分子量聚乙烯)，其抗磨损性显著增加[20]。这一种聚乙烯采用大剂量伽马射线强度通过降低聚乙烯分子的延展性来增加超高分子量聚乙烯的耐磨性[21]，而伽马射线和电子束射线可在聚乙烯表面产生自由基，部分自由基在交联中发生重组，影响了材料分子的链段，继而减少材料的塑性变形，同时大剂量的辐射也会加速超高分子量聚乙烯的氧化过程，间接地降低其使用寿命[22]。有研究显示将材料在熔点以下加热能够保存其机械性能和结晶度，但这并不能消除多余的自由基[23]；而将聚乙烯分子加热至熔点以上，结晶区消除，同时自由基表现出较好的移动性，继而提升辐射后超高分子量聚乙烯的氧化稳定性，但同时降低其结晶度[9]。有研究指出尽管交联能够减少材料的磨损量，但是辐射后超高分子量聚乙烯产生的微粒更小，且更具生物活性，而这些微粒能够增加关节溶骨的概率[8]。目前过度氧化造成的假体植入物材料老化仍然是一个尚待解决的问题。临床结果显示，关节植入物假体的氧化磨损率在移植后10年开始增加[24]。因此目前的关节假体衬垫中普遍加入抗氧化剂以延缓关节假体的氧化[24-28]。维生素E稳定型交联超高分子量聚乙烯(第4代超高分子量聚乙烯)同第3代一样采用大量辐射使聚乙烯分子交联，并使用维生素E取代惰性气体作为填充剂，这在增强超高分子量聚乙烯稳定性及耐磨性的同时，增强了抗氧化性，以达到延长植入假体寿命的目的。维生素E不仅可以取代惰性气体，且低浓度维生素E对人体无明显的不良反应[29-30]。然而维生素E稳定型交联超高分子量聚乙烯的力学性能很大程度上受到维生素E浓度的影响：当维生素E浓度低于0.4%时，其力学性能无明显变化[12，30]，而当维生素E浓度为0.8%时，其弹性系数和抗张强度明显下降，而伸展率和冲击强度仍旧保持不变[12]。但也有研究显示维生素E稳定型交联超高分子量聚乙烯具有更高的抗张强度、抗屈强度、断裂延伸率及抗疲劳强度，尤其是在浓度超过0.1%时[31-33]。 2.2 维生素E稳定型交联超高分子量聚乙烯的合成方式现将维生素E融合进超高分子量聚乙烯的方式主要有2种。第1种是辐射交联超高分子量聚乙烯后，将维生素E弥散入超高分子量聚乙烯[33-34]。通过这种方式融合维生素E需要2个步骤，第1步将辐射后的超高分子量聚乙烯掺杂进维生素E，第2步将其放入惰性气体进一步均化[33-34]。其中后一步骤尤为重要。这种合成方式中维生素E没有参与超高分子量聚乙烯的辐射过程，超高分子量聚乙烯的交联效率能够不被限制。更重要的是，合成后的维生素E浓度未受到交联密度的影响。但由于维生素E在40 ℃水温中融合超高分子量聚乙烯存在饱和限度，致使其浓度最高只能达到约0.7%[25]。从2007年起该种方式生产的维生素E稳定型交联超高分子量聚乙烯已应用于临床[10-11，22，33-34]。第2种方式是先将液态下的维生素E同超高分子量聚乙烯树脂粉末混合，然后将混合物由特定模型固定成近似于植入物形态，同时进行辐射产生交联[30，35-37]。通过这种方法能够在制作植入物的过程中维生素E浓度更加均匀，且制作时间明显缩短[38]。但是这种方式中，他由于存在维生素E，使辐射致交联效率降低[36]。因此，维生素E的浓度和辐射的剂量必须限制，以同时获得较好的抗磨损强度和抗氧化能力。一般建议混合物中维生素E的浓度不超过0.3%[39]。近来一些研究显示维生素E稳定型交联超高分子量聚乙烯的结构强度及抗疲劳强度能够通过一些补充手段得到提高，如通过高温将维生素E融合进超高分子量聚乙烯[34]。 2.3 维生素E作为抗氧化剂的作用原理维生素E作为氧化剂的作用原理是双重的，不仅可以提高照射后超高分子量聚乙烯的抗氧化性能，而且能够提高其抗疲劳强度[23，30，33，40-42]。维生素E能与自由基结合，降低超高分子量聚乙烯的氧化率，从而达到保护超高分子量聚乙烯的目的[37，43]。在高温或高纯度的氧气中，维生素E稳定型交联超高分子量聚乙烯会反而会比伽马射线消毒或高剂量辐射后的超高分子量聚乙烯更加稳定[23，33，40]。 2.4 维生素E稳定型交联超高分子量聚乙烯的应用进展作为最新一代的超高分子量聚乙烯，维生素E稳定型交联超高分子量聚乙烯并未大量开展体内实验。Wolf等[44]通过体外实验证实，维生素E稳定型交联超高分子量聚乙烯及0.8%维生素E的伽马消毒超高分子量聚乙烯均无明显细胞毒反应及遗传毒性反应。Fu等[38]通过傅里叶变换红外光谱学分析得出维生素E能明显提升超高分子量聚乙烯的抗氧化性，同时发现维生素E的热降解物质在交联辐射后仍然可以附着在聚乙烯物质上。Banche等[45]利用表皮葡萄球菌观察得出维生素E稳定型交联超高分子量聚乙烯有减少细菌趋化的能力，可提高关节假体抗细菌感染的能力，延长假体远期存活率。Schwiesau等[46]采用维生素E稳定型交联超高分子量聚乙烯作为关节假体模拟全膝关节置换的衬垫，对其进行了平地行走、上下楼梯及屈膝动作的试验。经过500万次的机械模拟试验后，没有一例假体的组成部件发生结构损坏。同时，关节假体的磨损率为(5.62±0.53) mg/每百万次，较之前的文献报道也有明显下降。此试验说明，维生素E能够延缓关节假体材料的老化过程，降低假体材料磨损，从而延长假体材料的寿命。"

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